Gene and protein expression profiles of prostaglandin E2 receptor subtypes in the human corpus cavernosum

Abstract

Prostaglandin E1 leads to penile erection, mainly via prostaglandin E2 (EP) receptors. This study aimed to identify the expression profile of EP receptor genes in human corpus cavernosum. Using the quantitative real-time reverse transcription polymerase chain reaction, the mRNA levels of EP receptor subtypes were measured. In addition, expressions of EP receptor subtype proteins were determined by immunohistochemical method. Among the four subtypes, EP4 receptor mRNA expression was the highest, and EP2 receptor mRNA followed, whereas EP1 and EP3 receptor mRNAs were hardly observed. Expression level of EP4 receptor mRNA was significantly higher than that of EP2 receptor mRNA. Expression of both EP2 and EP4 receptor proteins were clearly detected in the cavernous smooth muscle. These results may suggest that EP4 receptor plays an important role among four EP receptor subtypes for relaxation of smooth muscle in the human corpus cavernosum.

Pathways to relaxation of corporal smooth muscle

“…The EP receptor exists as four subtypes: EP1, EP2, EP3, and EP4 [35]. Komuro et al [36] have recently shown that EP4, followed by EP2, exhibits the highest mRNA expression in human CCSM, suggesting that along with EP2, the EP4 receptor may also have a role in CCSM relaxation. Interestingly, PGE1 self-injection is particularly effective in men with diabetes and in patients who do not respond to oral PDE5 inhibitors [37,38].…”

Pharmacological and Functional Characterization of Novel EP and DP Receptor Agonists: DP1 Receptor Mediates Penile Erection in Multiple Species

“…Membranes (20 mg/well) prepared from HEK293 cells expressing human DP1 receptor were incubated with 2.5 nM [5,6,8,9,12,14, was determined with 10 mM of unlabeled PGD 2 (Cayman, Ann Arbor, MI, USA). Reactions were terminated by filtration through GF/C glass fiber Unifilter plates (Whatman) that were previously soaked in 0.5% PEI.…”

“…The composition of the cavernosal (erectile) tissue and the tone of the vascular smooth muscle within the penis are critical determinants of erectile function [3,4]. The vasodilatory prostanoids PGE 2 and PGD 2 are both synthesized by penile cavernosal tissue, and exert their effects through functional EP and DP receptors [5][6][7][8][9][10].…”

“…The pharmacological and molecular characterization of EP and DP receptors is complicated by the existence of multiple receptor subtypes and splice variants that couple to different G‐proteins. In human penile corpus cavernosum, EP1, EP2, EP3‐type I, EP3‐type II, EP4, and DP receptors have been detected [6,7,9,10]. EP1 (G q ‐coupled) and EP3‐type I (G i ‐coupled) receptors mediate smooth muscle contraction by stimulating phospholipase C (inositol phosphate pathway) or inhibiting adenylyl cyclase, respectively [1,2].…”

Anesthetic drug propofol inhibits the expression of interleukin‑6, interleukin‑8 and cyclooxygenase‑2, a potential mechanism for propofol in suppressing tumor development and metastasis

“…PGE2 is an important downstream protein of COX-2 and is involved in the promotion of tumor cell growth and angiogenesis (21)(22)(23)(24). VEGF is also an important cytokine in the genesis and development of tumors (25).…”